Is the intravascular administration of mesenchymal stem cells safe? Mesenchymal stem cells and intravital microscopy. Microvasc Res

Department of Cardiac Surgery, Medical Faculty, University of Rostock Schillingallee 35, 18055 Rostock, Germany.
Microvascular Research (Impact Factor: 2.13). 03/2009; 77(3):370-6. DOI: 10.1016/j.mvr.2009.02.001
Source: PubMed


We investigated the kinetics of human mesenchymal stem cells (MSCs) after intravascular administration into SCID mouse cremaster vasculature by intravital microscopy. MSCs were injected into abdominal aorta through left femoral artery at two different concentrations (1 x 10(6) or 0.2 x 10(6) cell). Arterial blood velocity decrease by 60 and 18% 1 min after high/low dose MSCs injection respectively. The blood microcirculation was interrupted after 174+/-71 and 485+/-81 s. Intravital microscopy observation and histopathologic analysis of cremaster muscles indicated MSCs were entrapped in capillaries in both groups. 40 and 25% animals died of pulmonary embolism respectively in both high and low MSCs dose groups, which was detected by histopathologic analysis of the lungs. Intraarterial MSCs administration may lead to occlusion in the distal vasculature due to their relatively large cell size. Pulmonary sequestration may cause death in small laboratory animals. MSCs should be used cautiously for intravascular transplantation.

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    • "However, their efficiency of homing as a function of local tissue properties is unclear (19). The risk of intravascular transplantation of cultured MSCs should also be taken into consideration (20,21). MSCs can be delivered by site-directed approaches in the treatment of impaired tissue (22). "
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    ABSTRACT: Hyposalivation is an intractable side‑effect of radiotherapy for head and neck cancer. It is caused by the irreversible loss of acinar cells and decreased saliva secretion. However, this situation severely compromises the quality of life of affected patients. Currently, there is no effective treatment for this condition. In the present study, we developed a novel approach to regenerate the function of the irradiation‑damaged salivary glands using human adipose tissue‑derived stem cell (hADSC) intraglandular transplantation. ZsGreen‑labeled hADSCs were adoptively transferred into Sprague‑Dawley (SD) rat submandibular glands immediately following exposure to 18 Gy irradiation. A higher salivary flow rate (SFR) was observed in the hADSC‑treated group. Tissue improvement, including angiogenesis, anti‑apoptosis and anti‑fibrosis, was detected in the hADSC‑treated glands as compared to the untreated glands. Quantitative reverse transcription PCR (RT-qPCR) revealed a significantly higher expression of vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), cyclooxygenase‑2 (COX‑2) and matrix metalloproteinase‑2 (MMP‑2) in the hADSC‑treated rats. Furthermore, immunohistochemical analysis indicated that the hADSCs had differentiated into acinar and ductal cells in the rat submandibular glands. Thus, our results suggest that hADSCs are able to regenerate irradiation‑damaged salivary glands through glandular transplantation.
    Full-text · Article · Jul 2014 · International Journal of Molecular Medicine
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    • "During ARDS, in addition to the deteriorated pulmonary function, there is accumulation of circulatory cells by an increase in the adherence to the endothelium. Furthermore, the large size of the mesenchymal stem cells (close to 100 μm in diameter) that circulate in the 10 μm microvessels of the lung increases the risk of pulmonary microemboli [42]. In addition, we decided to deliver the cells into only one lung leaving the other lung intact to reduce possible major complications. "
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    ABSTRACT: Acute respiratory distress syndrome (ARDS) is the most common cause of respiratory failure among critically ill subjects, sepsis and severe bacterial pneumonia being its most common causes. The only interventions that have proven beneficial are protective ventilation strategies and fluid conservation approaches. New therapies are needed to address this common clinical problem. Others and we have previously shown the beneficial effect of infusion of exogenous adult stem cells in different pre-clinical models of ARDS. In the present study endotoxin was infused intravenously into 14 sheep from which 6 received different doses of adult stem cells by intrabronchial delivery to evaluate the effect of stem cell therapy. After administration of endotoxin, there was a rapid decline in oxygenation to hypoxemic values, indicative of severe-to-moderate ARDS. None of the animals treated with saline solution recovered to normal baseline values during the 6 hours that the animals were followed. In contrast, sheep treated with a dose of 40 million adult stem cells returned their levels of oxygen in their blood to baseline two hours after the cells were infused. Similarly, improvements in carbon dioxide (CO2) clearance, pulmonary vascular pressures and inflammation were observed and confirmed by histology and by the decrease in lung edema. We concluded that instillation of adult non-hematopoietic stem cells can diminish the impact of endotoxin and accelerate recovery of oxygenation, CO2 removal and inflammation in the ovine model, making the use of adult stem cells a real alternative for future therapies for ARDS.
    Full-text · Article · Mar 2014 · Stem Cell Research & Therapy
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    • "However, the effect and adverse reactions arising from peripheral stem cell therapy have not been fully characterized [7-9]. Incidence of adverse reactions, including myocardial infarction and embolism following stem cell transplantation, have been reported [8,9]. High pulmonary entrapment of systemically administered stem cells limits their homing and, hence, effectiveness of cell therapy [10,11]. "
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    ABSTRACT: Recent studies have assessed the therapeutic potential and drawbacks of mesenchymal stem cells (MSCs). The adverse reactions of intravenous transplantation of bone marrow (BM)-derived MSCs were examined at varying doses and frequencies of administration.Nine healthy beagle dogs were purchased from a commercial laboratory. The dogs were distributed equally (n = 3 per group) and randomly into three groups. All dogs received allogeneic BM-derived MSCs: 2 x 106 once (group A), 2 x 107 once (group B), and 2 x 106 for three consecutive days (group C). Various laboratory examinations, multi-detector computed tomography features and histopathology were evaluated to clarify the clinical and diagnostic features of adverse reactions of MSCs administration, prior to receiving MSCs (pre procedure) and on days 1, 3, and 7 post transplantation. Only one dog had clinical signs during and after MSCs transplantation. Dogs receiving 2 x 106 MSCs showed increased numbers of lymphocytes but the total white blood cell counts were not elevated (P < 0.01). Multi-detector computed tomography (MDCT) revealed pulmonary parenchymal changes in one dog and histopathologic examination revealed pulmonary parenchymal edema and hemorrhage in four dogs. The presence of pulmonary thromboembolism was not detected in either examination. We considered the presence of pulmonary edema and hemorrhage as possible adverse reactions after intravenous MSCs transplantation; however these results should be cautiously interpreted.
    Full-text · Article · Mar 2014 · Acta Veterinaria Scandinavica
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